Two decades of excellent transplant survival for chronic granulomatous disease: a supraregional immunology transplant center report

Abstract

Chronic granulomatous disease (CGD), an inherited immunodeficiency resulting from defects in the reduced NAD phosphate oxidase complex rendering phagocytes deficient in producing the superoxide anion necessary for normal killing of bacterial and fungal microorganisms, leads to severe and recurrent infections, inflammatory granulomatous complications, and autoimmune diseases. 1 It is associated with substantial morbidity and premature death. Hematopoietic cell transplantation (HCT) is the only long-term curative therapy; however, historically, utility was limited by high rates of graft failure and transplant-related morbidity and mortality. Transplant survival and graft outcome have improved dramatically over the past 10 years as a result of reduced-toxicity conditioning (RTC) regimens, detailed graftselection hierarchy, superior HLA-matching technology, better cell-dosed grafts, greater availability of grafts, improved supportive care, and more effective antimicrobial therapy. We studied transplant survival post-HCT for CGD in a supraregional immunology transplant center in the United Kingdom.

<p>Geographic Variability and Pathogen-Specific Considerations in the Diagnosis and Management of Chronic Granulomatous Disease</p>

“…Outcomes have improved significantly over the last few decades with reported overall survival rates now consistently >90% in pediatric patients less than 14 years of age regardless of donor source. [92][93][94][95][96][97][98][99] Furthermore, pediatric patients who undergo HSCT have fewer infections, improved growth parameters, and higher quality of life measures compared to those treated conventionally. 100,101 Patients with intractable infection or autoinflammation at the time of HSCT and adolescents or young adults have traditionally been difficult to transplant with historically high rates of graft-versus-host disease (GVHD) and transplant-related mortality.…”

Urogenital Abnormalities in Adenosine Deaminase Deficiency

“…Recently, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation has established recommendations for the diagnosis and pre-emptive procedures that should be offered to all children and adolescents in Europe who undergo life-saving allogeneic SCT [12]. Emerging reports describe fertility and gonadal function in transplanted SCID [13][14][15], but actually, no specific studies on ADA-SCID have been performed. We recommend that these aspects deserve special attention considering the systemic manifestations of the condition (ADA-SCID) and the potential effects of its treatments on gonadal function.…”

Cellular Therapies in Chronic Granulomatous Disease

“…More recently, haploidentical TCR alpha-beta -/CD19-depleted grafts were shown to successfully achieve myeloid donor cell engraftment without inducing relevant GVHD (103)(104)(105). The advantage of these in-vitro T-cell depletion techniques is that chronic GVHD is rare (14,80,106).…”

“…Graft failure remained a problem occurring in 12% of the patients ( 74 ). Some centers have therefore started to add thiotepa to treosulfan to further reduce the risk of GF ( 80 ), probably at the expense of augmented gonadotoxicity ( 94 ).…”

“…More recently, haploidentical TCR alpha-beta -/CD19-depleted grafts were shown to successfully achieve myeloid donor cell engraftment without inducing relevant GVHD ( 103 – 105 ). The advantage of these in-vitro T-cell depletion techniques is that chronic GVHD is rare ( 14 , 80 , 106 ). In-vivo T-cell depletion strategies in haploidentical transplants include the use post-transplant cyclophosphamide (PT/CY) (50 mg/kg/day), administered on day+3 and day +4 ( 107 ).…”